Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

Buck, Nicole E.; Cheah, Daphne M. Y.; Elwood, Ngaire J.; Wright, Paul; Allen, Katrina J.

doi:10.1007/s12072-007-9039-9

Cited by 6 publications

(6 citation statements)

References 24 publications

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“…Copper accumulation is common in basal ganglion and contributes to the neurological impairment in patients with WD. Consistent with previous studies [ 13 , 14 ], BM cells transplantation, to some degree, reduced the copper accumulation in brain tissue. However, whether lowering copper levels can correct neurological symptoms was not evaluated in this study because neurological symptoms cannot be tested in tx mice [ 16 ].…”

Section: Discussionsupporting

confidence: 92%

“…Recently, several studies have reported that BM cells transplantation can partially correct liver disease in a WD model [ 13 , 14 ]. Only long-term (5 or 9 months) effects of BM cells transplantation in correcting liver injury have been highlighted in these studies.…”

Section: Discussionmentioning

confidence: 99%

“…Repopulation of normal BM cells in recipient livers has been well documented in models of WD [ 13 , 14 ]. Based on the previous literature [ 25 ], Sry genes in Y-chromosomes were used to verify the repopulation of donor cells in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…The major discrepancies mainly lie in the different study designs. BM cells transplantations were performed at 3 to 4 months, and the populations of donor cells and liver injury rescues were generally evaluated at 5 and 9 months post-transplant in the previous studies [ 13 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…BM cells transplantation can partially reduce liver copper levels and correct liver disease in tx mice at five months post-transplant, and the beneficial effects of BM cells transplantation are similar to those obtained from normal congenic liver cells [ 13 ]. More recently, BM cells transplanted into tx mice have been shown to engraft in the liver and produce partial metabolic disease correction via reducing liver copper and increasing ceruloplasmin oxidase activity, although this effect may not be sustained over a 9-month period post-transplant [ 14 ]. However, it still remains unclear when BM cells transplantation should be administrated to correct liver dysfunction in mice with WD.…”

Section: Introductionmentioning

confidence: 99%

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Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

et al. 2011

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BackgroundRecent studies have demonstrated that normal bone marrow (BM) cells transplantation can correct liver injury in a mouse model of Wilson disease (WD). However, it still remains unknown when BM cells transplantation should be administered. The aim of this study was to investigate the potential impact of normal BM cells transplantation at different stages of WD to correct liver injury in toxic milk (tx) mice.MethodsRecipient tx mice were sublethally irradiated (5 Gy) prior to transplantation. The congenic wild-type (DL) BM cells labeled with CM-DiI were transplanted via caudal vein injection into tx mice at the early (2 months of age) or late stage (5 months of age) of WD. The same volume of saline or tx BM cells were injected as controls. The DL donor cell population, copper concentration, serum ceruloplasmin oxidase activity and aspartate aminotransferase (AST) levels in the various groups were evaluated at 1, 4, 8 and 12 weeks post-transplant, respectively.ResultsThe DL BM cells population was observed from 1 to 12 weeks and peaked by the 4th week in the recipient liver after transplantation. DL BM cells transplantation during the early stage significantly corrected copper accumulation, AST across the observed time points and serum ceruloplasmin oxidase activity through 8 to 12 weeks in tx mice compared with those treated with saline or tx BM cells (all P < 0.05). In contrast, BM cells transplantation during the late stage only corrected AST levels from 4 to 12 weeks post-transplant and copper accumulation at 12 weeks post-transplant (all P < 0.05). No significant difference was found between the saline and tx BM cells transplantation groups across the observed time points (P > 0.05).ConclusionsEarly stage transplantation of normal BM cells is better than late stage transplantation in correcting liver function and copper metabolism in a mouse model of WD.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

et al. 2011

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Toxic milk mice models of Wilson’s disease

Hadrian

Przybyłkowski

2021

Mol Biol Rep

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Wilson’s disease (WD) is a rare genetic disorder inherited as an autosomal recessive trait. The signs and symptoms of this disease are related to dysfunctional ATP7B protein which leads to copper accumulation and cellular damage. The organs that are most commonly affected by WD are the liver and brain. The dysfunctional ATP7B homolog has previously been identified in many different species, including two naturally occurring murine models called toxic milk mice. The aim of this paper was to compare the toxic milk mouse described by Rauch (tx) to that from Jackson Laboratory (txJ) through a review of studies on these two groups of mice. The two mice strains differ in the type of carried mutation and the phenotype of the disease. The data of the studies showed that the tx mice developed mild chronic hepatitis but suffered severe organ destruction with faster progression to full-liver cirrhosis. No changes were noted in the neurological and behavioral status of this strain despite the described toxic accumulation of copper and neuronal destruction in their brain. On the other hand, though the Jackson toxic milk mice (txJ) also presented chronic hepatitis, the condition was a bit milder with slower progression to end-stage disease. Moreover, hepatocyte suitable to perform neurobehavioral research as their phenotype characterized by tremors and locomotor disabilities better corresponds with the cliniconeurological picture of the humans.

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Animal Models for Wilson Disease

Hüster

2019

Clinical and Translational Perspectives on WILSON DISEASE

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Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

Abstract: These results demonstrate that bone marrow transplants cannot maintain disease correction in a mouse model of mild hepatic damage, although initial copper metabolism correction was observed.

Cited by 6 publications

References 24 publications

Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

Early stage transplantation of bone marrow cells markedly ameliorates copper metabolism and restores liver function in a mouse model of Wilson disease

Toxic milk mice models of Wilson’s disease

Animal Models for Wilson Disease

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